Compositions and methods for the delivery of nucleic acids

Abstract

A nanosized complex includes siRNA and a compound comprising formula (I):

Having described the invention, we claim: 
     
       1. A nanosized complex comprising siRNA and a compound comprising formula (I): 
       
         
           
           
               
               
           
         
         wherein R 1  is an alkylamino group or a group containing at least one aromatic group; 
         R 2  and R 3  are independently an aliphatic group or a hydrophobic group; 
         R 4  and R 5  are independently H, a substituted or unsubstituted alkyl group, an alkenyl group, an acyl group, an aromatic group, polymer, a targeting group, or a detectable moiety; 
         a, b, c, and d are independently an integer from 1 to 10; and 
         pharmaceutically acceptable salts thereof, 
         wherein the siRNA inhibits expression of an oncogenic nucleic acid upon delivery of the nanosized complex to a cell. 
       
     
     
       2. The nanosized complex of  claim 1 , wherein R 1  comprises at least one of: 
       
         
           
           
               
               
           
         
         where R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14  are independently hydrogen, an alkyl group, a hydrophobic group, or a nitrogen containing substituent; and 
         e, f, g, i, j, k, and I, are an integer from 1 to 10. 
       
     
     
       3. The nanosized complex of  claim 1 , wherein R 2  and R 3  are independently a hydrophobic group derived from oleic acid or linoleic acid. 
     
     
       4. The nanosized complex of  claim 3 , wherein R 2  and R 3  are the same. 
     
     
       5. The nanosized complex of  claim 1 , wherein R 4  and R 5  are independently H, a substituted or unsubstituted polymer, a targeting group, or a detectable moiety. 
     
     
       6. The nanosized complex of  claim 1 , wherein a, b, c, and d are each 2. 
     
     
       7. The nanosized complex of  claim 1 , R 1  comprises CH 2 CH 2 NH 2 . 
     
     
       8. The nanosized complex of  claim 1 , wherein the compound is 
       
         
           
           
               
               
           
         
       
     
     
       9. The nanosized complex of  claim 1 , wherein polyethylene glycol is covalently attached to the compound. 
     
     
       10. The nanosized complex of  claim 1 , wherein the targeting group is covalently attached to the compound by a linker. 
     
     
       11. The nanosized complex of  claim 10 , wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethylene glycol group. 
     
     
       12. The nanosized complex of  claim 10 , wherein the targeting group comprises a peptide, a protein, an antibody, or an antibody fragment. 
     
     
       13. The nanosized complex of  claim 11 , wherein the linker comprises an acid labile bond. 
     
     
       14. A method of treating cancer in a subject in need thereof, the method comprising:
 administering to the subject a nanosized complex comprising siRNA and a compound comprising formula (I): 
 
       
         
           
           
               
               
           
         
         wherein R 1  is CH 2 CH 2 NH 2 ; 
         R 2  and R 3  are independently an aliphatic group or a hydrophobic group; 
         R 4  and R 5  are independently H, a substituted or unsubstituted alkyl group, an alkenyl group, an acyl group, an aromatic group, polymer, a targeting group, or a detectable moiety; 
         a, b, c, and d are independently an integer from 1 to 10; and pharmaceutically acceptable salts thereof, 
         wherein the siRNA inhibits expression of an oncogenic nucleic acid upon delivery of the nanosized complex to a cancer cell. 
       
     
     
       15. The method of  claim 14 , wherein R 2  and R 3  are independently a hydrophobic group derived from oleic acid or linoleic acid. 
     
     
       16. The method of  claim 14 , wherein the compound is